JPS5852995B2 - Method for producing furfural derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a general compound used as a synthetic intermediate for the compound (I) represented by the general formula (in the formula, R1 represents a nitro group and X represents an oxygen atom) and is useful as a pharmaceutical product. Formula (wherein R', R2, and X have the same meanings as above)
This invention relates to a method for producing a novel compound represented by:

The compound represented by the above general formula (I) is extremely effective as a drug having muscle relaxing effects, and its manufacturing method includes the method described in Ameriga Patent No. 4,341,5821 (1968), but this manufacturing method generally has poor yields and is not suitable for industrial use. It is difficult to say that this method is economically advantageous.

As a result of various studies, the present inventors have discovered a compound represented by the general formula (wherein R1 has the same meaning as above) and a compound represented by the general formula %formula% () (wherein R2 is a lower ano+4y group). and X has the same meaning as above) is reacted, or
Alternatively, compound (II) is reacted with a compound represented by the general formula % (in which R2 has the same meaning as above), and ) was found to be able to be produced in high yield by heating and cyclizing compound (g) obtained by reacting isocyanic acid with isocyanic acid.Based on this, the present invention completed.

That is, the present invention provides (1) a method for producing compound (g), characterized by reacting compound (n) and compound (l[); )
The present invention relates to a method for producing compound (g), which is characterized by reacting compound (V) with isocyanic acid.

The target compound (g) of the present application consists of compound (II) and compound (
It can be produced by reacting with I).

In this reaction, an excess molar amount of (I), generally about 1 to 5 molar amount, is preferably used with respect to 1 mole of general formula (■).

Usually, an appropriate inert solvent is used for the reaction itself, such as alcohols (e.g., methanol, ethanol, propatool, etc.) or dialkylformamides (e.g., dimethylformamide, diethylformamide, etc.). There is no need for this, and both may be reacted directly.

As the reaction temperature, an appropriate temperature between 00 and 200°C is selected.

In addition, the target compound (Vl) can be obtained by reacting compound (II) with hydrazinoacetate (IV) to form compound (V).
It can be produced by producing and reacting this with isocyanic acid.

In this reaction, (■) GV) 1 to 5 per mol
Although moles can be used, about 1 to 2 moles are usually preferred.

The reaction is carried out using a solvent that is inert to the reaction itself, such as (II) and (
Although the solvents described in reaction 1) are used, it is not always necessary to use a solvent and the two may be reacted directly.

It is preferable to use an appropriate reaction temperature between 0° and 200°C.

The compound (VI) thus produced is reacted with isocyanic acid to produce compound (VI).

The isocyanic acid used in this reaction has the general formula % () [where M represents an alkali metal (e.g., sodium, potassium) or alkaline earth metal (e.g., calcium, barium), and X is the same as above. It may also be produced by acidifying a compound represented by [having a meaning].

Generally, it is preferable to react (1) and - under acidic conditions, and the acids used for this purpose include organic acids such as acetic acid or propionic acid, or mineral acids such as hydrochloric acid and sulfuric acid.

Generally, it is preferable to carry out the reaction using 11 to 10 moles of VI per 1 mole of (V).

This reaction is usually carried out using a solvent that is inert to the reaction itself, such as water (
It is carried out in the solvents and the like described for the reaction of It) and (I), or in a mixture thereof.

Alternatively, a mixed solvent of these solvents and the above acids can be used, or the acid itself can be used as the solvent.

The reaction temperature is usually selected to be an appropriate temperature between 200 and 150°C.

The product thus produced can usually be collected as a crystalline substance when the reaction solution is neutralized.

The present compound (g) can be purified by purification means known per se, such as chromatography or recrystallization, as necessary.
Although it can be modified to a higher purity, it can generally be used as it is as a raw material for the next step.

Compound (I) can be produced by heating the compound (g) thus obtained.

The purpose of this reaction can be achieved by heating (g) to an appropriate temperature selected from about 30°C to 200°C.

At this time, no solvent is used, or if necessary, a solvent inert to the reaction itself, such as dialkylformamides (e.g., dimethyl- or diethyl-formamide, etc.), dialkyl sulfoxides (e.g., dimethyl- or diethyl-formamide, etc.),
It can also be carried out in sulfoxide, etc.).

Usually, good results are obtained by adding about 1 to 10 moles of the condensing agent to 1 mole of (VI).

(I) produced in this manner can be collected in any range by separation and purification methods known per se, such as recrystallization and chromatography.

The total yield from normal (II) is about 70% or more and about 90%.

Example 1 Ethyl hydrazinoacetate hydrochloride Q, 928.9 2 ml of water
Add 0.53i of potassium isocyanate to the solution and dissolve.
Leave to stand for 15 minutes to make a solution of ethyl N'-rubamoylhydrazinoacetate. Add 4N-hydrochloric acid to this solution and adjust the pH to 2.
3, then 10 m of ethanol, 0.434 g of P-nitrophenylfurfural was added, and after heating under reflux for 10 minutes, water was added to collect the precipitated crystals, and N-(5-(P-
Crystals of nitrophenylfurfurylideneamino]-N-rubamoylglycine ethyl ester are obtained.

Yield: 97.2% Motojima is recrystallized from hydrous dimethylformamide to give yellow needles with a melting point of 234-236°C.

Elemental analysis C16H14N406 Calculated value C53,33,'H4,48,N 15.5
5 Experimental values C53, 47, H4, 39, N 15.53
Example 2 (1) 5-(P-nitrophenyl)furfural 0
．． Add 0.34 g of hydrazinoacetic acid ethyl ester hydrochloride to 44 g of 10 ml of ethanol, heat for several minutes to form a solution, leave at room temperature for a while, and add saturated hydrogen carbonate solution I.
- Add IJum solution and extract with ethyl acetate.

The ethyl acetate layer is washed with water, dried (Na2SO4), and the solvent is distilled off to obtain crystals of N-(5-(p-nitrophenyl)furfurylideneamino)glyneedle ethyl ester.

Red-orange needles, melting point 120-122°C.

(2) N-(5-(P-nitrophenyl)furfurylideneamino)glycine ethyl ester produced above 0
．． 32. ? Add 0.48 g of potassium isocyanate to 5 ml of acetic acid solution under ice-cooling in three portions, stir for 10 minutes, and then add water to collect the precipitated crystals.

Washed sequentially with water and acetone and dried.
Crystals of nitrophenylfurfurylideneamino]-N-carbamoylglycine ethyl ester are obtained.

Melting point 233-236°C0

Claims (1)

[Scope of Claims] 1 A compound represented by the general formula (wherein R1 represents a nitro group) and a compound represented by the general formula NH2-N-CH, C00R2 X=C-NH2 (wherein R2 represents a lower alkyl group, X represents an oxygen atom)
A method for producing a compound represented by the general formula (wherein I (1, R2, and X have the same meanings as above)). 2. A compound represented by the general formula (wherein R1 represents a nitro group) and the general formula A compound represented by the general formula (in the formula, R1 and R2 have the same meanings as above) is produced by reacting hydrazinoacetic esters represented by the formula % (in the formula, R2 represents a lower alkyl group). A method for producing a compound represented by the general formula (wherein R' j R2 has the same meaning as above, and X represents an oxygen atom), which comprises reacting this with isocyanic acid.